Regina Scholz
Charité
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Publication
Featured researches published by Regina Scholz.
Journal of Magnetism and Magnetic Materials | 2001
Andreas Jordan; Regina Scholz; Klaus Maier-Hauff; Manfred Johannsen; Peter Wust; Jacek Nadobny; Hermann Schirra; Helmut K. Schmidt; S. Deger; Stefan A. Loening; Wolfgang R. Lanksch; Roland Felix
Magnetic fluid hyperthermia (MFH) selectively heats up tissue by coupling alternating current (AC) magnetic fields to targeted magnetic fluids, so that boundaries of different conductive tissues do not interfere with power absorption. In this paper, a new AC magnetic field therapy system for clinical application of MFH is described. With optimized magnetic nanoparticle preparations it will be used for target-specific glioblastoma and prostate carcinoma therapy.
International Journal of Hyperthermia | 2005
Manfred Johannsen; Uwe Gneveckow; L. Eckelt; Annelie Feussner; N. Waldöfner; Regina Scholz; S. Deger; Peter Wust; Stefan A. Loening; Andreas Jordan
The aim of this pilot study was to evaluate whether the technique of magnetic fluid hyperthermia can be used for minimally invasive treatment of prostate cancer. This paper presents the first clinical application of interstitial hyperthermia using magnetic nanoparticles in locally recurrent prostate cancer. Treatment planning was carried out using computerized tomography (CT) of the prostate. Based on the individual anatomy of the prostate and the estimated specific absorption rate (SAR) of magnetic fluids in prostatic tissue, the number and position of magnetic fluid depots required for sufficient heat deposition was calculated while rectum and urethra were spared. Nanoparticle suspensions were injected transperineally into the prostate under transrectal ultrasound and flouroscopy guidance. Treatments were delivered in the first magnetic field applicator for use in humans, using an alternating current magnetic field with a frequency of 100 kHz and variable field strength (0–18 kA m−1). Invasive thermometry of the prostate was carried out in the first and last of six weekly hyperthermia sessions of 60 min duration. CT-scans of the prostate were repeated following the first and last hyperthermia treatment to document magnetic nanoparticle distribution and the position of the thermometry probes in the prostate. Nanoparticles were retained in the prostate during the treatment interval of 6 weeks. Using appropriate software (AMIRA), a non-invasive estimation of temperature values in the prostate, based on intra-tumoural distribution of magnetic nanoparticles, can be performed and correlated with invasively measured intra-prostatic temperatures. Using a specially designed cooling device, treatment was well tolerated without anaesthesia. In the first patient treated, maximum and minimum intra-prostatic temperatures measured at a field strength of 4.0–5.0 kA m−1 were 48.5°C and 40.0°C during the 1st treatment and 42.5°C and 39.4°C during the 6th treatment, respectively. These first clinical experiences prompted us to initiate a phase I study to evaluate feasibility, toxicity and quality of life during hyperthermia using magnetic nanoparticles in patients with biopsy-proven local recurrence of prostate cancer following radiotherapy with curative intent. To the authors’ knowledge, this is the first report on clinical application of interstitial hyperthermia using magnetic nanoparticles in the treatment of human cancer.
International Journal of Hyperthermia | 2007
Manfred Johannsen; Uwe Gneveckow; Kasra Taymoorian; Burghard Thiesen; N. Waldöfner; Regina Scholz; Klaus Jung; Andreas Jordan; Peter Wust; Stefan A. Loening
Purpose: To investigate the treatment-related morbidity and quality of life (QoL) during thermotherapy using superparamagnetic nanoparticles in patients with locally recurrent prostate cancer. Materials and Methods: Ten patients with biopsy-proven locally recurrent prostate cancer following primary therapy with curative intent and no detectable metastases were entered on a prospective phase I trial. Endpoints were feasibility, toxicity and QoL. Following intraprostatic injection of a nanoparticle dispersion, six thermal therapy sessions of 60 min duration were delivered at weekly intervals using an alternating magnetic field. National Cancer Institute (NCI) common toxicity criteria (CTC) and the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-PR25 questionnaires were used to evaluate toxicity and QoL, respectively. In addition, prostate specific antigen (PSA) measurements were carried out. Results: Maximum temperatures up to 55°C were achieved in the prostates at 25–30% of the available magnetic field strength. Nanoparticle deposits were detectable in the prostates one year after thermal therapy. At a median follow-up of 17.5 months (3–24), no systemic toxicity was observed. Acute urinary retention occurred in four patients with previous history of urethral stricture. Treatment-related morbidity was moderate and QoL was only temporarily impaired. Prostate-specific antigen (PSA) declines were observed in eight patients. Conclusions: Interstitial heating using magnetic nanoparticles was feasible and well tolerated in patients with locally recurrent prostate cancer. Deposition of nanoparticles in the prostate was highly durable. Further refinement of the technique is necessary to allow application of higher magnetic field strengths.
Biomaterials | 2009
Frank K. H. van Landeghem; Klaus Maier-Hauff; Andreas Jordan; Karl T. Hoffmann; Uwe Gneveckow; Regina Scholz; Burghard Thiesen; Wolfgang Brück; A. von Deimling
Patients with glioblastoma multiforme (GBM), the most common primary brain tumor in adults, have still a poor prognosis though new strategies of radio- and chemotherapy have been developed. Recently, our group demonstrated the feasibility, tolerability and anti-tumoral effects of a newly developed therapeutic approach, termed thermotherapy using magnetic nanoparticles or magnetic fluid hyperthermia (MFH), in a murine model of malignant glioma. Currently, the efficacy of MFH is being evaluated in a phase II study. Here, we report on post-mortem neuropathological findings of patients with GBM receiving MFH. In brain autopsies the installed magnetic nanoparticles were dispersed or distributed as aggregates within geographic tumor necroses, restricted in distribution to the sites of instillation. Therefore, our results underscore the need for multiple trajectories of instillation. The typical GBM necrosis with pseudopalisading was free of particles. Dispersed particles and particle aggregates were phagocytosed mainly by macrophages whereas glioblastoma cells showed an uptake to a minor extent. MFH therapy further promotes uptake of nanoparticles in macrophages, likely as a consequence of tumor inherent and therapy induced formation of necrosis with subsequent infiltration and activation of phagocytes. We did not observe bystander effects of MFH such as sarcomatous tumour formation, formation of a sterile abscess or foreign body giant cell reaction. Furthermore, all patients did not present any clinical symptoms related to possible adverse effects of MFH.
Medical Physics | 2004
Uwe Gneveckow; Andreas Jordan; Regina Scholz; Volker Brüß; Norbert Waldöfner; J Ricke; Annelie Feussner; Bert Hildebrandt; Beate Rau; Peter Wust
Magnetic fluid hyperthermia (MFH) is a new approach to deposit heat power in deep tissues by overcoming limitations of conventional heat treatments. After infiltration of the target tissue with nanosized magnetic particles, the power of an alternating magnetic field is transformed into heat. The combination of the 100 kHz magnetic field applicator MFH 300F and the magnetofluid (MF), which both are designed for medical use, is investigated with respect to its dosage recommendations and clinical applicability. We found a magnetic field strength of up to 18 kA/m in a cylindrical treatment area of 20 cm diameter and aperture height up to 300 mm. The specific absorption rate (SAR) can be controlled directly by the magnetic field strength during the treatment. The relationship between magnetic field strength and the iron normalized SAR (SAR(Fe)) is only slightly depending on the concentration of the MF and can be used for planning the target SAR. The achievable energy absorption rates of the MF distributed in the tissue is sufficient for either hyperthermia or thermoablation. The fluid has a visible contrast in therapeutic concentrations on a CT scanner and can be detected down to 0.01 g/l Fe in the MRI. The system has proved its capability and practicability for heat treatment in deep regions of the human body.
Cell Stress & Chaperones | 2000
Markus Hantschel; Karin Pfister; Andreas Jordan; Regina Scholz; Reinhard Andreesen; Gerd Schmitz; Helga Schmetzer; Wolfgang Hiddemann; Gabriele Multhoff
Abstract A tumor-selective cell surface localization of heat shock protein 70 (Hsp70), the major heat-inducible member of the Hsp70 group, correlates with an increased sensitivity to lysis mediated by human natural killer (NK) cells and, therefore, might be of clinical relevance. With the exception of mammary carcinomas, an Hsp70 plasma membrane expression was found on freshly isolated human biopsy material of colorectal, lung, neuronal, and pancreas carcinomas, liver metastases, and leukemic blasts of patients with acute myelogenous leukemia. Since normal tissues and bone marrow of healthy human individuals do not express Hsp70 on the cell surface, Hsp70 can be considered as a tumor-selective structure in vivo. Furthermore, we demonstrate that autologous, Hsp70-positive leukemic blasts can be killed by NK cells stimulated with low doses of interleukin 2 plus recombinant Hsp70 protein.
Journal of Endourology | 2004
Manfred Johannsen; Andreas Jordan; Regina Scholz; Martin Koch; Michael Lein; Serdar Deger; Jan Roigas; Klaus Jung; Stefan A. Loening
PURPOSE To examine the feasibility and potential of magnetic fluid hyperthermia (MFH) as a minimally invasive method for hyperthermia treatment of prostate cancer. MATERIALS AND METHODS Orthotopic Dunning R3327 prostate tumors were induced in 20 male Copenhagen rats. The animals either received MFH treatment following intratumoral administration of magnetic fluids or were used as either tumor growth controls for determination of iron distribution in selected organs or as histologic controls without MFH treatment. The MFH treatments were carried out at 45 degrees C or 50 degrees C using an AC magnetic field applicator system designed for small animals. RESULTS Sequential treatments with MFH were possible following a single intratumoral injection of magnetic fluid. Intratumoral temperatures of 50 degrees C and more were obtained and were monitored online using fluoro-optic thermometry. Four days after MFH treatments, 79% of the injected dose of ferrites was still present in the prostate. CONCLUSIONS The successful intraprostatic nanoparticle infiltration and stable steady-state intratumoral treatment temperatures demonstrate the feasibility of MFH in a prostate cancer model. Efficacy and survival benefit must be confirmed in further experiments.
Oncogene | 2002
Ilja Demuth; Susanne Rothe; Regina Scholz; Andreas Jordan; Carsten Grötzinger; Detlev Schindler; Markus Grompe; Karl Sperling
The accumulation of DNA repair proteins at the sites of DNA damage can be visualized in mutagenized cells at the single cell level as discrete nuclear foci by immunofluorescent staining. Formation of nuclear foci in irradiated human fibroblasts, as detected by antibodies directed against the DNA repair protein MRE11, is significantly disturbed by the presence of the viral oncogene, SV40 large T-antigen. The attenuation of foci formation was found in both T-antigen immortalized cells and in cells transiently expressing T-antigen, indicating that it is not attributable to secondary mutations but to T-antigen expression itself. ATM-mediated nibrin phosphorylation was not altered, thus the disturbance of MRE11 foci formation by T-antigen is independent of this event. The decrease in MRE11 foci was particularly pronounced in T-antigen immortalized cells from the Fanconi anaemia complementation group FA-D2. FA-D2 cells produce essentially no MRE11 DNA repair foci after ionizing irradiation and have a significantly increased cellular radiosensitivity at low radiation doses. The gene mutated in FA-D2 cells, FANCD2, codes for a protein which also locates to nuclear foci and may, therefore, be involved in MRE11 foci formation, at least in T-antigen immortalized cells. This finding possibly links Fanconi anaemia proteins to the frequently reported increased sensitivity of Fanconi anaemia cells to transformation by SV40. From a practical stand point these findings are particularly relevant to the many studies on DNA repair which exploit the advantages of SV40 immortalized cell lines. The interference of T-antigen with DNA repair processes, as demonstrated here, should be borne in mind when interpreting such studies.
International Journal of Cancer | 2000
Gabriele Multhoff; Karin Pfister; Claus Botzler; Andreas Jordan; Regina Scholz; Helga Schmetzer; Ralf Burgstahler; Wolfgang Hiddemann
In vitro, tumor‐selective Hsp70 plasma membrane localization correlates with increased sensitivity to lysis mediated by a subpopulation of human natural killer (NK) cells that adhere to plastic following cytokine stimulation. In the present study, we analyzed the capacity of adoptively transferred human NK cells in SCID/beige mice for local tumor control and prevention of metastatic dissemination of Hsp70‐expressing CX+ and non‐expressing CX– tumors following orthotopic (o.t.) injection. Both tumor sublines were derived by cell sorting of the original cell line, CX2, and thus exhibit an identical MHC and adhesion molecule expression pattern but differ with respect to Hsp70 plasma membrane expression. Viability of adherent, human NK cells in SCID/beige mice up to 18 days and the capacity to migrate have been demonstrated. Growth of Hsp70‐expressing and non‐expressing CX+ and CX– tumor cells was completely suppressed when 10 × 106 NK cells were injected into the i.p. cavity on day 4 after inoculation of 2.5 × 106 tumor cells. Although a single injection of 5 or 2.5 × 106 NK cells was not sufficient to suppress tumor growth completely in all mice, the reduction in size of CX+ tumors was significantly greater than that of CX– tumors. To mimic the clinical situation, ex vivo stimulated NK cells were injected i.v. on day 4 after o.t. injection of tumor cells. Under these conditions, growth of Hsp70‐expressing primary tumors and metastases was suppressed. If CX– tumor cells were injected, 3 of 9 mice developed Hsp70‐negative primary tumors. However, none of these mice developed distant metastases. In summary, our data indicate that Hsp70 acts as a recognition structure for adherent NK cells in a SCID/beige mouse model. Int. J. Cancer 88:791–797, 2000.
Journal of Nanoparticle Research | 2003
Andreas Jordan; Thomas Rheinländer; Norbert Waldöfner; Regina Scholz
Magnetic fractionation was applied to a common magnetic fluid based on superparamagnetic iron-oxide nano-particles with core radius of 5nm. The fractions collected were investigated with respect to particle-sizes and the influence of fractionation on the specific absorption rate, in order to optimize magnetic fluids for the application in hyperthermia.